The characterisation of the uptake of microparticulates across intestinal lymphoid tissue

Howard, Kenneth Alan (1994) The characterisation of the uptake of microparticulates across intestinal lymphoid tissue. PhD thesis, University of Nottingham.

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Abstract

Poly(lactide-co-glycolide) (PLG) biodegradable microparticles were evaluated as an oral delivery system for immunisation against equine influenza virus. Model particulates (fluorescent polystyrene and gold labelled polystyrene) were used to characterise the route and mechanism of intestinal uptake. Peyer's patches were found to be the site of particulate intestinal absorption characterised by phagocytosis at the M cell surface. Microparticles were found within intercellular compartments indicating a paracellular route for the transit of microparticles from lumen to lymph. A quantitative method of counting the number of microparticles passing into the lymph in both the superior mesenteric and thoracic lymph ducts indicated levels of intestinal uptake high enough to deliver vaccines via this route.

PLG microparticles encapsulating equine influenza virus were prepared by the process of solvent evaporation. The immune responses were evaluated in mice after either systemic or oral immunisation of Balb\c mice using formalin treated equine influenza (Prague 56 H7N7) either encapsulated in PLG biodegradable microparticles or free in solution. Using the single-radial- immunodiffusion test, the haemagglutinin integrity of the microencapsulated influenza was found to be preserved during the microencapsulation process. When administered systemically the microencapsulated virus induced raised levels of anti-influenza IgG antibody in serum that were comparable with those obtained with the virus in solution. Oral administration of the microencapsulated virus induced raised levels of anti-influenza IgA antibody in saliva as well as levels of anti-influenza IgG comparable to those obtained after parenteral injection. Raised levels (compared to preimmune levels) of anti-influenza antibodies in both the systemic circulation and mucosal secretions indicates that orally administered microencapsulalated equine influenza virus represents a practical method of immunisation against influenza.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Davies, Bob
O'Hagan, Derek
Thomas, Norman
Keywords: equine influenza vaccines, microparticulates, PLG microparticles, nanoparticles, intestinal lymphoid tissue, oral medicine
Subjects: R Medicine > RM Therapeutics. Pharmacology
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 11675
Depositing User: EP, Services
Date Deposited: 23 Nov 2010 09:44
Last Modified: 24 Sep 2016 10:55
URI: http://eprints.nottingham.ac.uk/id/eprint/11675

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